We propose a two year, two part screening/interview and prospective followup study of HTLV-III infection in heterosexual intravenous drug users (IVDUs) in San Francisco, in collaboration with major treatment programs. 1. Screening/interview study. We will screen 1000-1200 IVDUs in each year of study, including one third of the annual treatment program intake, by ELISA with Western Blot confirmation. Subjects will be interviewed for demographics and risk factors by ourselves and collaborators. We will obtain (1) serial measurement of HTLV-III prevalence in the city and in specific programs; (2) assessment of risk-reduction interventions; (3) identification of behavioral risk factors; and (4) recruitment of seropositives for prospective study. 2. Prospective study. We will accumulate a cohort of 150 IVDUs and matched seronegative controls and follow them at 6-8 month intervals for clinical and laboratory status. We will (1) analyze rates of progression to clinical AIDS, ARC, and immune abnormalities; (2) explore cofactors and predictors of pregression; and (3) compare the natural history of HTLV-III infection in IVDUs with our parallel cohort of seropositive homosexual men.